The large majority of patients having B-cell malignancies, including chronic lymphocytic leukemia (CLL), will die from their disease. One approach to treating these patients is to genetically modify T cells to target antigens expressed on tumor cells through the expression of chimeric antigen receptors (CARs). CARs are antigen receptors that are designed to recognize cell surface antigens in a human leukocyte antigen-independent manner. Attempts in using genetically modified cells expressing CARs to treat these types of patients have met with very limited success. See for example, Brentjens et al., 2010, Molecular Therapy, 18:4, 666-668; Morgan et al., 2010, Molecular Therapy, published online Feb. 23, 2010, pages 1-9; and, Till et al., 2008, Blood, 112:2261-2271.
While CARs can trigger T-cell activation in a manner similar to an endogenous T-cell receptor, a major impediment to the clinical application of this technology to date has been limited in vivo expansion of CAR+ T cells, rapid disappearance of the cells after infusion, and disappointing clinical activity (Jena, et al., Blood, 2010, 116:1035-1044; Uckun, et al. Blood, 1988, 71:13-29). Methods of generating genetically modified T cells for administration to humans have the potential to produce unwanted contaminants that may negatively impact the persistence and function of the genetically modified T cells after administration.
Thus, there is a need in the art for analyzing transduced T cells for their suitability for administration to a human subject, through the detection of contaminants that may negatively impact the persistence and function of genetically modified cells. The present invention addresses this need.